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Showing posts with label Fertility. Show all posts
Showing posts with label Fertility. Show all posts

Traps from delicious foods? Eat right and have better sperm




Do you like wearing a tight pants or putting your laptop on your thighs? These habits may affect the quality of your sperm. Besides, five types of drinks/foods may harm your reproductive system. Let’s check and keep in mind!

According to <<Epicurious>>, if the quality of your sperm is not good, it may affect your family plan. To maintain the good quality of sperm, the uptakes of following drinks/foods must be controlled.

 1. Alcohol
Alcohols dehydrates the water in our bodies, and increases the risk of obesity, and reduces the mobility of sperms. We suggest not drinking alcohol more than once per week, and therefore the bodies can metabolize the alcohol. But if you have severe reproductive problem, it is better to quit alcohol.






2. Processed meat products
Bacon, ham and burger are delicious, but these processed meat products usually contain high proportion of saturated fat and hormone residues, which harm the quality of sperm. If you like meat, have the “fresh” one.







3. Sweet Drinks
Bubble milk tea or other sweet drinks contain high proportion of sugarstimulating pancreas to release more insulin, and they increases the risk of obesity. Sweet drinks reduce both the quantity and quality of sperm. It’s better for us to drink water.






4. High-fat dairy products
Milk, cheese and other dairy products can provide protein, calcium and other nutrients. But the high fat contained in these products may harm male’s reproductive system. Also, pesticide or hormone residues should be concerned in some dairy products.





5. Fruits with pesticide residues
Some of the fruits or vegetables may have pesticide residues, especially apples, grapes, strawberries, spinach, cucumbers, etc. We suggest choosing organic fruits and vegetables to decrease the risk.





Stay away from bad habits and unhealthy foods/drinks. Get your sperm good! 


小暐 小暐 Author

What should we know about male infertility


Like the infertility issues in females, 
male fertility correlates with the age, lifestyle, and individual background. 
If you are aware of these factors, 
you may know more about your own body state.


With the dramatic change in recent society, people tend to start family late. We usually choose to pursue career first, and put starting our own family at the second priority. This decision made more people encounter the infertility problems at their late 30s and 40s of age. More and more studies demonstrated that the quality of oocyte declines with increasing female age. Thus oocyte cryopreservation for the social reason becomes more popular. How about the men? Several studies also found that the mean age of fathering men showed increased since 1993 to date. Meanwhile, the percentage of male factor in the entire population with fertility problem is increasing as well. The following 4 questions are frequently asked by our male cases,





1. Should semen analysis be routinely clinical testing?


Reproductive potential gradually declines with advanced paternal age, but the declining speed is not as fast as maternal ovaries. The semen analysis is the most common method to check the general sperm quality. Some studies indicated that there is significant decrease in semen volume, sperm concentration, sperm motility and sperm morphology among older men. The pregnancy rate in the men at 40s displayed 10% down than that in the men at 30s. Thus the males with advanced age and abnormal semen parameters have higher risk for the infertility issue. Should the semen analysis be routine testing? Maybe NOT. Only the couple who has failed to conceive for ≧1 year is recommended.





2. Should PGS (preimplantation genetic screening) be performed in the men at advanced age? 

The rate of aneuploid embryo is higher in women at advanced age (≧36 years old), and thus PGS becomes an option for them to choose the embryo with normal chromosomal dosage. Is it possible that the aneuploid embryo derived from the sperm with advanced paternal age ? Hassold et al. demonstrated that one of the cause for trisomy 21 is paternal chromosome nondisjunction, and it accounted for 20% of the entire population with trisomy 21. A more-recently scientific article showed that significantly increasing aneuploid rate in embryos from the older men and men with oligozoospermia. It appears that suboptimal sperm can be a source of embryo aneuploidy. However, the correlation of paternal age and embryo aneuploidy is not as strong as that of maternal age. For those with partner at advanced maternal age, or with the recurrent miscarriage history or family inherited disease, PGS/PGD is recommended. Generally, the paternal age is not the sole indication for PGS.





3. What should the older father know?

Several reports showed the children with older fathers are more likely to develop certain pathologies, such as the schizophrenia. The rate of autism spectrum disorders slightly increases as well. For the father themselves, some medical comorbidities do affect the fertility, like heart disease and chronic medicines of hypertension. It could lead to erectile dysfunction and benign prostatic hypertrophy.



4. Should males cryopreserve their sperm for social reason?


The sperm motility could be halved after cryopreservation. For men with known fertile issue, cryopresevation may induce sperm DNA damage. Since the correlation between fertility and male age is not as strong as the female age, there is no need to cryopreserve sperm for the social reason, and the state of frozen sperm is not comparable to the fresh sperm.

Beyond examinations, healthy diet and lifestyle do help the fertility. It's not necessary to cryopreserve sperm at young age. If the body stays good, the quality of sperm may remain for a long time.


小暐 小暐 Author

Distance makes the hearts grow stronger





No distance is too far for the two loving hearts


If the love is true, 

the distance is just the power of making people grow.





As the metro pulled out of the station, the man wrote "I love you" on the window. His girlfriend left on the platform, and still gazed into his eyes. It was always not easy to say goodbye for them, especially the following flashbacks after separation.


In the patients at our fertility center, some couples are living apart by necessity. Their husbands could be in the army, fisherman, or overseas businessman. The wives need to face the daily challenges bravely and maintain their home fully.



She was 37 years old and married her husband 7 years ago. They had no children yet. Before visiting us, she had tried IVF three times and undergone several embryo transfers at the other clinics. The ending of this journey seemed still unclear. The doctor arranged the hormone tests of AMH (as an index of ovarian reserves), Prolactin (PRL), and Thyroid stimulating hormone (TSH), to evaluate her body status.


Her PRL value was higher than the reference, suggesting that it might interferes the ovulation. Usually, the elevated PRL could be found in the women with breast feeding. However, the PRL could also increase in the women lack of sleep or under stress. The elevated PRL causes hypogonadism, possible anovulatory, and a decrease in menstruation.


The doctor gave her some medications for the hyperprolactinemia, and subsequent IVF treatment. With a declined AMH value as 1.63 ng/ml, the individualized controlled ovarian stimulation protocol was designed. Since her and her husband lived apart, the doctor planned the strategy of egg collection to fit their schedule. The capacity of female eggs are highly correlated with the maternal age. Therefore, the doctor recommends them to collect at least 15 eggs to increase the possibility of success pregnancy. If she would like to have two children, more eggs could be required.




Entering the IVF cycle again made her feel lonely and stressful. After work, she took the bus from Keelung to Hsinchu, and walked to our clinic. The commuting would take three hours every time. Thus she visited us late, and was always the last one at the clinic suite. The obvious exhaust and anxiety showed on her face. She was afraid that she could not catch the lastest bus up. We all knew that it was such a difficulty to her.


Five mature eggs were collected in the first cycle. In this egg retrieval, the doctor found some unsynchronized follicles with small size. Thus she went through the subsequent duoble-OPU to get the surplus eggs. Until she had 8 eggs, her and her husband decided to give a first try.
Her husband came to our clinic for sperm collection and then the embryologists thawed her eggs to perform the following fertilization. They got 2 blastocysts and transferred the one grading as 5AB freshly.


She got pregnant by this good blastocyst!





Although this journey was hard to her, she insisted to continue. With such a brave heart, she is ready to be a mother.
小暐 小暐 Author

Does the mild stimulation improve embryo euploid rate in diminished ovarian reserve women?


The psychological and financial burden of IVF increases while the ovarian function declines.

If the frequency of injection decreases, would the patients still have enough embryos for transfer?




Women with diminished ovarian reserve (DOR, which was defined as Anti-mullerian hormone < 2 ng/ml and Antral follicle count ≦ 5 here), are confronted with insufficient ovarian reserve. Although controlled ovarian stimulation (COS) is an efficient treatment for infertility, it involves costly injections for the purpose of retrieving more oocytes during cycle. In order to evaluate the efficiency of different ovarian stimulation protocols in DOR patients, the chromosome constitution identified by using NGS platform was used as a parameter for assessing the embryo quality.



During January 2015 to June 2016, 52 patients (mean age: 38.1 years) with AMH < 2 ng/ml and AFC≦5, were randomly assigned to undergo strong stimulation (long-acting r-FSH and short-acting r-FSH with daily injections), or mild stimulation (short-acting r-FSH with every-other-day injections), or mini stimulation (clomiphene citrate only or natural cycle). A total of 139 embryos from 86 IVF/PGS cycles were biopsied on culturing day 5 or 6, and then analyzed on NGS platform (Miseq®).




Compared with strong stimulation group, mild and mini stimulation groups result in fewer retrieved oocytes per cycle. (Strong:6.1# Ovum; Mild:4# Ova; Mini:1.9# Ova). Moreover, studied patients with advanced maternal age (≧38ys) undergoing mini stimulation showed a tendency to possess more embryos available for biopsy in total retrieved oocytes (Mini: 64.4% v.s. Strong: 35.9%). And the euploid rate of mild and mini stimulation groups were higher than that of the strong stimulation group (Mild plus Mini: 27.6% v.s. Strong: 20.8%). It is known that the euploid rate decreased with increasing maternal age, and mini stimulation seems to have the potential to improve the euploid rate in the patients with DOR.



The preliminary data suggests that different ovarian stimulation strategies could affect the number of retrieved oocytes and chromosomal abnormality of embryos. A friendly ovarian stimulation strategy should concern both the efficiency and the feeling for patients.
小暐 小暐 Author

If I still have my periods, can I be pregnant?




"If I still have my periods, can I be pregnant?"


It is a common question at fertility centers. The specialist clarified that having periods does not mean having ovulations. Many women with advanced age thought that having periods equals to having potential to be pregnant. The fact is that older the age is, worse the egg quality is. That is why the women with advanced maternal age are harder to be pregnant.







Since the social style and economic environment are changing, more people do not expect to start their family in the early life. Getting married later made the infertility issue become more serious. In Taiwanese records, one seventh couples are suffering with infertility (around 15% of population).


Over half of infertile couples choose to undergo assisted reproduction

According to the Taiwan ministry of Health and Welfare reports, the number of IVF babies increases annually, and it increased twofold in the last decade. Five of every ten infertile couples would choose assisted reproduction programs to have babies including IUI and IVF.


Clinically, abnormal vaginal bleeding or anovulatory menstruation could mislead people to believe they still have potential to be pregnant naturally. Not like normal menstrual bleeding in an ovulatory cycle is a result of progesterone withdrawal bleeding, anovulatory bleeding is commonly caused by estrogen breakthrough bleeding.
The cycle lengths of females with anovulatory menstruation showed different degrees: most have prolonged cycle lengths, but some have regular or even frequent menses (though the amount of fluid is comparably fewer).



To sum up, the irregular menstruation is highly correlated with infertility due to anovulation. The clinical indications of anovulation could be hormone disorders (e.g. PCOS, hyperprolactinemia, thyroid disorders), upstream reasons such as hypothalamic dysfunction, or age issue (e.g. ovulation dysfunction, perimenapause).








In the age issue, women with age at 25 years have highest pregnancy rate; with age over 40 only have half or lower of highest pregnancy rate. Women suffering with infertility problem was around 6% in the group spanning 20-24 years, 9% in the group spanning 25-29, 15% in the group spanning 30-34, 30% in the group spanning 35-39, and 64% in the group spanning 40-44. Beyond 45 years of age, the pregnancy rate of IVF patients were quite low. Thus the most appropriate age of taking IVF program is under 35 years, and the clinical outcomes also displayed more favorable in this group. 





 

Stork Fertility Center Stork Fertility Center Author

Oocyte spindle and embryo ploidies



From oocyte retrieval to blastocyst cryopreservation, the best timing to do fertilization is always an important issue in the IVF realm. The techniques of ICSI, or IMSI, can help the embryo technician select the sperm with the best morphology to increase the fertilization rate. After the development of spindle microscope (an modified microscope which can observe the spindle of oocyte), the question of "when to fertilize?" has emerged.



In the newly-released article of Science, the author explained the reason of higher chromosomal aneuploidy in human oocytes in comparison with the other human somatic cells, and mouse oocytes. Holubcova el al. developed a time-lapse system combing with vital stain of human oocyte to record the oocyte maturation process (from GVBD to MII).





They found that the time from GVBD (geminal vesicle breakdown) to initial chromosome congression (~16 hrs) was significantly longer than those in the other mammal meiosis (~3-5 hrs). Instead of mediating by centrosomes or MTOCs (microtubule organizing centers), the mediator in human oocyte meiosis was chromosome itself (Ran-GTP).


Lacking of centrosomes or MTOCs led spindle formation in human oocytes intrinsically unstable and error-prone, and then it made the higher aneuploid rate due to maternal origin in the following embryo propagation.



Of the application in IVF, this time-lapse video of oocyte maturation may provide the users of spindle microscope more information about the accurate timing to do the fertilization, or to cryopreserve the MII eggs.

Original article:
Zuzana Holubcova, Martyn Blayney, Kay Elder, and Melina Schuh
Science 2015;348:1143-1147.



Stork Fertility Center Stork Fertility Center Author

Spending NTD 500,000 (~USD 16,666) on IVF, I got a baby with Down syndrome




Ms. Chen, a 43-year-old woman, has spent NTD 500,000 (~USD 16,666) on the assisted reproductive treatments. She got married late, and finally got pregnant after several IVF cycles. However, the report of amniocentesis displayed abnormal in the 16th weeks of gestation. The baby has chromosome 21 trisomy, which has known as Down syndrome. Ms. Chen and her husband was very disappointed at the clinic suite, and repeatedly asked to the doctor " Is it real? Could it be any mistake in the report?"




Both the usual ages of marriage and pregnant are increasing in Taiwan. There are more and more mothers-to-be with advanced ages at GYOPD. Many women got married in their 40s, and they were hurried to catch up the "progress"—making a baby. Few people could get pregnant naturally at these ages, and so many couples chose to undergo IVF to have babies. Additionally, the risk of babies with Down syndrome is increasing as well.

Averagely, one with Down syndrome per 800 newborns was in Taiwan. The risk is 50 times higher in the women of 45 years than those of 25 years. 

Ms. Chen took amniocentesis at the 16 weeks of gestation. The report was released 2 weeks after. When she got the bad news and must take the induction, it was already at her 20 weeks of gestation. The psychological and physical stress were increasing with the gestation weeks.

The prenatal testing for Down syndrome include invasive methods, such as amniocentesis (at 16th weeks), and non-invasive methods, such as NIPT/NIFTY (at 10~12 weeks).

With the improvement of molecular technology, the NIPT uses the mothers' blood to test the cell-free fetal chromosomes, including trisomy 21, trisomy 18, trisomy 13, and sex chromosome abnormalities. The accuracy and sensitivity are high in the above chromosomes.









Since the trends of getting married and pregnant late were obvious in Taiwan, and thus the women with advanced maternal age should think more about the biological schedule.



Stork Fertility Center:

1. Over 43 years, the live birth rate per retrieval cycle was under 5%, and the miscarriage rate was over 30% according to the data of Stork Fertility Center.



2. Three strategies for the women with different ages:




3. Since the Taiwanese government only provides the supplementary grant of amniocentesis to the women over 35 years, over 80% of babies with Down syndrome were delivered by the younger mothers ( under 35 years of age). The policy misleads people to ignore the importance of prenatal testing in the younger women.

Stork Fertility Center Stork Fertility Center Author

How to define the "Poor Ovarian Response"?


"Why do I have only a few follicles developed in this cycle?"


"Why my stimulated follicles seems less than the last cycle?"


Some patients had poor response to the controlled ovarian stimulation, and thus they underwent the treatment almost per month to collect available oocytes. These patients were defined as the group of potential " poor ovarian response (POR)." In 2011, the European Society of Human Reproduction and Embryology (ESHRE) defined these patients based on the standard criteria, which were called "Bologna Criteria,"



At least two of the following three features must be present:
i.
Advanced maternal age ( 40 years), or any other risk factors for POR
ii.
A previous POR ( 3 oocytes with a conventional stimulation protocol)
iii
An abnormal ovarian reserve test (ORT, i.e. AFC < 5-7 or AMH < 0.5-1.1 ng/ml)

However, the clinical identification of POR are still very difference, since not all the patients with POR met the above description.


In 2014, an Australian researcher, Venetis, indicated that the Bologna Criteria can't define the POR group clearly due to its complicated statistics. Another researcher, Papathanasiou, from United Kingdom, thought that the POR group shouldn't be defined by a simple dichotomy, but by an integrated assessment.
These concepts from different areas may be affected by the racial characteristics. In Taiwan, the Chang-Kung medical research group did a retrospective analysis to evaluate the applicability of Bologna Criteria to the Taiwanese POR patients,

Study subjects: the cycle with retrieval oocyte 3

Study time span: Jan, 2001 ~ Sep, 2014

Sample size: 855 cycles (under 40 years of age: 589 cycles; over 40 years of age: 266 cycles)

According to the following table, four factors displayed significant effect to the clinical outcomes: age, primary/secondary infertility, number of mature oocytes, grading of transferred embryo


They further compared the embryologic and clinical characteristics between the group over 40 years and under 40 years, and found that the maternal age was the most crucial factor in the patientsthe fertilization rate, embryo grading (blastocyst stage), implantation rate, clinical pregnancy rate were better in the group under 40 years than those in the group over 40 years.

Due to the individual diversity in the POR group defined by Bologna Criteria, the universal definition may not be appropriate to all the potential POR patients. As it mentioned above, the maternal age may be more important than the other affecting factors. Thus the applied treatments in the patients must be modified according to their age.


References:
1.  2015 TSRM: Evaluation of the Bologna criteria for women of different age: Cohort study of women with extremely low oocyte retrieval cycles.
2.  The Bologna criteria for poor ovarian response: the good, the bad and the way forward. Human Reproduction, 2014.
3.  Implementing the ESHRE ‘poor responder’ criteria in research studies: methodological implications. Human Reproduction,29(9) 1835-8, 2014.
Stork Fertility Center Stork Fertility Center Author

A sign of euploid embryo



Although the PGS is well validated and prevalent in the IVF realm, the cost and invasive method are still the main concerns in the patients. Besides, not every embryo is tolerant to the biopsy procedure.

1/8 couple suffered by infertile issue in the world

17,000 IVF cycles per year in Taiwan

1.5-fold growth of IVF babies during 1998 to 2012 in Taiwan





Advanced maternal age, male factor, premature ovarian failure, repeated miscarriage, and unexplained cause are several indications of infertility.


In addition, chromosome anomaly of embryo was found as one of the main reasons to the pregnancy failure. Except doing the preimplantation genetic screening (PGS) to see the chromosome constitution directly, several researches tried to find the indicators of emrbyo ploidy from many parameters in embryo development. Some scientific reports displayed the correlation between embryo morphology and chromosome constitution. However, the significant relationship remains controversy.



Another article focused on correlation between chromosome aneuploidy and blastulation time (time of blastocyst formation). It indicated that the euploid blastocysts formed faster than the aneuploid blastocysts with single or multiple chromosome aneuploidy.


In a report released in the 2015 Annual Meeting of Taiwan Society of Reproductive Medicine (TSRM), a research group found that the embryo with early blastulation (EB) in 95-97 hours post insemination (hpi) displayed higher euploid rate than those with EB later 95-97 hpi (47.6% vs. 35.1%), though the following clinical outcomes showed no significant differences between these two groups.




Further investigations of embryo development and chromosome constitution were still necessary. And the system of time-lapse culture may help us to observe the process more accurately.

References
1.     TSRM Annual Meeting 2015
2.     Samer Alfarawatiet al., Fertility and Sterility, Vol. 95, No. 2, February 2011
3.     Alison Campbellet al., Reproductive BioMedicine Online (2013) 26, 477– 485

Stork Fertility Center Stork Fertility Center Author

Oocyte activation


We just discussed one issue of male factors in the infertility realm—azoospermia. Actually the entire proportion of male factors in the infertility indications is around 35-40%, and they were divided into the following groups.

 


By using several assisted reproductive techniques, such as intracytoplasmic sperminjection (ICSI) and intracytoplasmic morphologically selected sperm injection (IMSI), the average fertilization rate was raised up to 70%-80%. However, complete fertilization failure or very-low fertilization rate still occurred in around 1-5% of IVF-ICSI cycles. In this case, the issue of incomplete oocyte activation was concerned. The interactions between oocyte and sperm during fertilization was displayed as follows.



 



As the figure illustrated, the signal transduction began from the acrosome (sperm head) reaction. The phospholipase C zeta (PLCζ) was released from acrosome into the oocytoplasm, and thus the phosphotidylinositol 4,5-bisphosphate (PIP2) was decomposed as diacylglycerol (DAG) and inositol trisphosphate (IP3). Then the IP3 combined to the IP3 receptors on the endoplasmic reticulum and induced the release of stored calcium ions (Ca2+). The released Ca2+ flows activated the oocyte and turned on its cell cycle.


Globozoospermia (sperms with round head) is one of common causes in complete fertilization failure. It was because that round-head sperms lack acrosomes, and then no PLCζ turn on the pathway of oocyte activation.
Comparing the Ca2+ oscillation between the sperms resulted in higher and lower fertilization rate in the ICSI cycles, a Ca2+ oscillation with higher amplitude and frequency was induced by the sperms resulted in higher fertilization rate. In contrast, the sperms with lower fertilization rate either was unable to induce the oscillation, or induced an oscillation with weaker amplitude and frequency only.




Artificial oocyte activation (AOA) was reported as one way to solve the complete fertilization failure. This procedure can be done by three different methods:
1. Chemical AOA: Ca2+ ionophores (A23187), ionomycin, puromycin, and so on. (most common)
2. Electric AOA: using electric shock to induce the Ca2+ oscillation
3. Mechanic AOA: injection of Ca2 into the oocyte directly. (less common)


References:
· Kashir J, Heindryckx B, Jones C, De Sutter P, Parrington J, Coward K. Oocyte activation, phospholipase C zeta and human infertility. Hum Reprod Update. 2010 Nov-Dec;16(6):690-703.
· Yoon SY, Jellerette T, Salicioni AM, Lee HC, Yoo MS, Coward K, Parrington J, Grow D, Cibelli JB, Visconti PE et al. Human sperm devoid of PLC, zeta 1 fail to induce Ca2+ release and are unable to initiate the first step of embryo development. J Clin Invest 2008; 118:3671–3681.
· Mohammad Hossein Nasr-Esfahani, Mohammad Reza Deemeh, Marziyeh Tavalaee. Artificial oocyte activation and intracytoplasmic sperm injection. Fertility and Sterility, Published online: April 27 2009.
· John Zhang, Chia-Woei Wang, Anna Blaszcyzk, James A Grifo, Jean Ozil, Elisa Haberman, Alexis Adler, Lewis C Krey. Electrical activation and in vitro development of human oocytes that fail to fertilize after intracytoplasmic sperm injection. Fertility and Sterility, Published in issue: September 1999.



Stork Fertility Center:

1. Complete fertilization failure occurs around 1% or lower in the clinical patients with indications of male-factor according to our records. Most of these patients have limited amount of available oocytes (MII) to be fertilized. The real percentage of patients with oocyte inactivation is even lower than 1%.
2. The general procedures of ICSI include two steps to assist oocyte activation: immobilization of sperm by pressing its tail; sucking and penetration of the oocyte membrane. By this procedure, the sperm cytosolic factor is released and injected into the oocytoplasm to induce the Ca2+ oscillation. However, if globozoospermia (no sperm cytosolic factor inside) or abnormal receptor expression or Ca2+ concentration in the oocyte, the artificial oocyte activation is then recommended.
3. Indeed the fertilization rate increased by using of AOA, but several scientific reports also demonstrated that the rate of following embryo arrest during culture and abortion rate after transfer also correlated with the treatment of AOA. The benefits of AOA remains controversial. 
Stork Fertility Center Stork Fertility Center Author